According to new research, the body remembers the stress of heart failure and appears to cause recurrent heart failure, along with other related health problems. Researchers have discovered that heart failure leaves a “stress memory” in the form of changes in the modification of the DNA of hematopoietic stem cells, which are involved in the production of blood and immune cells called macrophages. These immune cells play an important role in protecting heart health. However, a key signaling pathway (a chain of molecules that transmits signals within a cell), called transforming growth factor beta (TGF-β), in hematopoietic stem cells was suppressed during heart failure, which negatively affected to the production of macrophages. Improving TGF-β levels could be a new avenue for treating recurrent heart failure, while detecting stress memory buildup could provide an early warning system before it occurs.
Healthier lives and greater well-being are among the United Nations’ global Sustainable Development Goals. Positively, a recent study shows that life expectancy worldwide is projected to increase by approximately 4.5 years by 2050. Much of this is due to public health efforts to prevent disease and improve survival from disease. , such as cardiovascular disorders. However, heart disease remains the leading cause of death worldwide, with an estimated 26 million people affected by heart failure.
Once heart failure has occurred, it tends to come back along with other health problems, such as kidney and muscle problems. Japanese researchers wanted to understand what causes this recurrence and deterioration of other organs, and whether it can be prevented.
“Based on our previous research, we hypothesize that recurrence may be caused by the stress experienced during heart failure that accumulates in the body, particularly in hematopoietic stem cells,” explained project professor Katsuhito Fujiu of the Faculty of Medicine at the University of Tokyo. Hematopoietic stem cells are found in the bone marrow and are the source of blood cells and a type of immune cells called macrophages, which help protect heart health.
By studying mice with heart failure, the researchers found evidence of a stress signature in the epigenome, that is, chemical changes occurred in the DNA of the mice. An important signaling pathway, called transforming growth factor beta, which is involved in the regulation of many cellular processes, was suppressed in the hematopoietic stem cells of mice with heart failure, leading to the production of dysfunctional immune cells.
This change persisted over an extended period of time, so when the team transplanted bone marrow from mice with heart failure into healthy mice, they found that the stem cells continued to produce dysfunctional immune cells. These latter mice subsequently developed heart failure and became prone to organ damage.
“We call this phenomenon stress memory because the stress of heart failure is remembered for a long period of time and continues to affect the entire body. Although other types of stress could also imprint this stress memory, we believe that stress induced by heart failure heart failure is particularly significant,” Fujiu said.
The good news is that by identifying and understanding these changes in the TGF-β signaling pathway, new avenues are now being opened for potential future treatments. “Completely new therapies could be considered to prevent the buildup of this stress memory during heart failure hospitalization,” Fujiu said. “In animals with heart failure, additionally supplementing active TGF-β has been shown to be a potential treatment. Correcting the epigenome of hematopoietic stem cells could also be a way to deplete stress memory.”
Now that it has been identified, the team hopes to develop a system that can detect and prevent the buildup of stress memory in humans, with the long-term goal of being able to not only prevent the recurrence of heart failure, but also detect the condition earlier. that it can be fully developed.